维基百科

起始点识别复合物

在分子生物学中，起始点识别复合物[2]（origin recognition complex, ORC）是指一种真核生物体内的含有多个亚基、与DNA结合的复合物。它与DNA通过一种ATP依赖性的方式相连，使得DNA复制得以启动。该复合物的几个亚基分别由ORC1（英语：ORC1）、ORC2（英语：ORC2L）、ORC3（英语：ORC3L）、ORC4（英语：ORC4L）、ORC5（英语：ORC5L）、ORC6（英语：ORC6L）基因编码[3][4][5]。起始点识别复合物不仅在真核生物DNA复制期间存在，在整个细胞周期的其余时段也与复制起点结合[6]。起始点识别复合物对DNA复制的启动来说不可或缺[7][8][9]。与复制起点结合的起始点识别复合物使得复制前复合物（英语：pre-replication complex）（pre-replication complex, pre-RC）得以组装。复制前复合物的组分包括Cdc6（英语：Cdc6）、Tah11(亦称Cdt1（英语：Cdt1）），以及MCM2（英语：MCM2）-MCM7（英语：MCM7）复合物[10][11][12]。复制前复合物在G1期的组装对于S期的DNA复制前的DNA复制许可（英语：licensing factor）至关重要。不经过许可，DNA复制就无法进行[13][14][15]。周期素依赖性蛋白激酶Cdc28（英语：Cdc28）能磷酸化Orc2、Orc6、Cdc6，以调节DNA复制的起始（包括封锁G2/M期的复制再启动），进而达到调节细胞周期的目的[6][16][17][18]。

起始点识别复合物（ORC）亚基2
鉴定
标志ORC2
PfamPF04084（旧版）
InterPro（英语：InterPro）IPR007220
起始点识别复合物亚基（ORC）亚基3N-端
鉴定
标志ORC3_N
PfamPF07034（旧版）
InterPro（英语：InterPro）IPR010748
起始点识别复合物亚基（ORC）亚基6
鉴定
标志ORC6
PfamPF05460（旧版）
InterPro（英语：InterPro）IPR008721
CDC6在DNA复制起始中可能发挥的作用[1]

在酵母细胞中，起始点识别复合物亦参与交配型（英语：Mating of yeast）相关的基因位点HML和HMR的沉默[7][8][9]。起始点识别复合物参与HML、HMR位点的染色质组装，让Sirl沉默蛋白装入染色质中，使得这两个位点沉默[9][19][20]。

Orc1以及Orc5这两个起始点识别复合物的亚基均与ATP结合，不过只有Orc1具有ATP酶活性[21]。Orc1与ATP的结合使起始点识别复合物得以与DNA结合，对细胞的生存至关重要[12]。另外，Orc1的ATP酶活性亦与复制前复合物的生成有关[22][23][24]。而Orc5与ATP的结合则使得起始点识别复合物能作为一个整体稳定存在。只有Orc1到Orc5这5个亚基对复合物与复制起点的结合是必需的。Orc6则能使复制前复合物在合成之后能稳定存在[25]。对起始点识别复合物内部的相互作用的研究表明，Orc2、Orc3、Orc6可能组成了复合物的核心部分[6]。

参考文献

  1. ^ Borlado LR, Méndez J. CDC6: from DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis. February 2008, 29 (2): 237–43. PMID 18048387. doi:10.1093/carcin/bgm268. 
  2. ^ 译名来自：朱玉贤等. 《分子生物學》 第三版. 2008: pp.49. ISBN 978-7-04-022214-2. 
  3. ^ 医学主题词表（MeSH）：Origin+Recognition+Complex
  4. ^ Dutta A, Bell SP. Initiation of DNA replication in eukaryotic cells. Annu. Rev. Cell Dev. Biol. 1997, 13: 293–332. PMID 9442876. doi:10.1146/annurev.cellbio.13.1.293. 
  5. ^ Chesnokov IN. Multiple functions of the origin recognition complex. Int. Rev. Cytol. 2007, 256: 69–109. PMID 17241905. doi:10.1016/S0074-7696(07)56003-1. 
  6. ^ 6.0 6.1 6.2 Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T. Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res. December 2007, 7 (8): 1263–9. PMID 17825065. doi:10.1111/j.1567-1364.2007.00298.x. 
  7. ^ 7.0 7.1 Bell SP, Stillman B. ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature. May 1992, 357 (6374): 128–34. PMID 1579162. doi:10.1038/357128a0. 
  8. ^ 8.0 8.1 Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B. The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell. November 1995, 83 (4): 563–8. PMID 7585959. doi:10.1016/0092-8674(95)90096-9. 
  9. ^ 9.0 9.1 9.2 Gibson DG, Bell SP, Aparicio OM. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells. June 2006, 11 (6): 557–73. PMID 16716188. doi:10.1111/j.1365-2443.2006.00967.x. 
  10. ^ Rao H, Stillman B. The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc. Natl. Acad. Sci. U.S.A. March 1995, 92 (6): 2224–8. PMC 42456  . PMID 7892251. doi:10.1073/pnas.92.6.2224. 
  11. ^ Rowley A, Cocker JH, Harwood J, Diffley JF. Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. EMBO J. June 1995, 14 (11): 2631–41. PMC 398377  . PMID 7781615. 
  12. ^ 12.0 12.1 Speck C, Chen Z, Li H, Stillman B. ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nat. Struct. Mol. Biol. November 2005, 12 (11): 965–71. PMC 2952294  . PMID 16228006. doi:10.1038/nsmb1002. 
  13. ^ Kelly TJ, Brown GW. Regulation of chromosome replication. Annu. Rev. Biochem. 2000, 69: 829–80. PMID 10966477. doi:10.1146/annurev.biochem.69.1.829. 
  14. ^ Bell SP, Dutta A. DNA replication in eukaryotic cells. Annu. Rev. Biochem. 2002, 71: 333–74. PMID 12045100. doi:10.1146/annurev.biochem.71.110601.135425. 
  15. ^ Stillman B. Origin recognition and the chromosome cycle. FEBS Lett. February 2005, 579 (4): 877–84. PMID 15680967. doi:10.1016/j.febslet.2004.12.011. 
  16. ^ Weinreich M, Liang C, Chen HH, Stillman B. Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc. Natl. Acad. Sci. U.S.A. September 2001, 98 (20): 11211–7. PMC 58709  . PMID 11572976. doi:10.1073/pnas.201387198. 
  17. ^ Nguyen VQ, Co C, Li JJ. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature. June 2001, 411 (6841): 1068–73. PMID 11429609. doi:10.1038/35082600. 
  18. ^ Archambault V, Ikui AE, Drapkin BJ, Cross FR. Disruption of mechanisms that prevent rereplication triggers a DNA damage response. Mol. Cell. Biol. August 2005, 25 (15): 6707–21. PMC 1190345  . PMID 16024805. doi:10.1128/MCB.25.15.6707-6721.2005. 
  19. ^ Triolo T, Sternglanz R. Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature. May 1996, 381 (6579): 251–3. PMID 8622770. doi:10.1038/381251a0. 
  20. ^ Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J. The origin recognition complex, SIR1, and the S phase requirement for silencing. Science. June 1997, 276 (5318): 1547–51. PMID 9171055. doi:10.1126/science.276.5318.1547. 
  21. ^ Klemm RD, Austin RJ, Bell SP. Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell. February 1997, 88 (4): 493–502. PMID 9038340. doi:10.1016/S0092-8674(00)81889-9. 
  22. ^ Klemm RD, Bell SP. ATP bound to the origin recognition complex is important for preRC formation. Proc. Natl. Acad. Sci. U.S.A. July 2001, 98 (15): 8361–7. PMC 37444  . PMID 11459976. doi:10.1073/pnas.131006898. 
  23. ^ Bowers JL, Randell JC, Chen S, Bell SP. ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. Mol. Cell. December 2004, 16 (6): 967–78. PMID 15610739. doi:10.1016/j.molcel.2004.11.038. 
  24. ^ Randell JC, Bowers JL, Rodriguez HK, Bell SP. Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol. Cell. January 2006, 21 (1): 29–39. PMID 16387651. doi:10.1016/j.molcel.2005.11.023. 
  25. ^ Semple JW, Da-Silva LF, Jervis EJ, Ah-Kee J, Al-Attar H, Kummer L, Heikkila JJ, Pasero P, Duncker BP. An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. EMBO J. November 2006, 25 (21): 5150–8. PMC 1630405  . PMID 17053779. doi:10.1038/sj.emboj.7601391. 

拓展阅读

此条目包含有源于Pfam以及InterPro的属于公有领域的文本 IPR007220

此条目包含有源于Pfam以及InterPro的属于公有领域的文本 IPR010748

此条目包含有源于Pfam以及InterPro的属于公有领域的文本 IPR008721

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